POS0505 NO EXCESS MORTALITY IN CONTEMPORARY UNDIFFERENTIATED ARTHRITIS, IN CONTRAST TO RHEUMATOID ARTHRITIS; A STUDY WITH A FOLLOW-UP OF AT LEAST 10 YEARS
Authors: M. Verstappen, T. Huizinga, A. Van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2022)

Background Undifferentiated arthritis (UA) is traditionally considered an early phase of rheumatoid arthritis (RA), 1 and management strategies of RA are often transferred to UA-patients assuming outcomes are comparable. Importantly, the UA population changed with the introduction of 2010 RA criteria as part of the conventional UA population became classified as RA. Consequently, contemporary UA-patients (not fulfilling the 1987 nor 2010 RA-criteria) are largely autoantibody negative and present with relatively mild disease. 2 Subsequently, contemporary UA might no longer represent a group of patients in a pre-phase of RA but a population with intrinsically different characteristics than RA. We therefore hypothesized that mortality, a long term outcome which is increased in RA, is not increased in contemporary UA. Objectives To asses mortality rates in contemporary UA-patients, and to compare this to RA and conventional UA during at least 10 years of follow up. Methods We studied 860 conventional UA-patients (no 1987 RA-criteria or other diagnosis), 561 contemporary UA-patients (no 1987/2010 RA-criteria or other diagnosis) and 762 RA-patients according to the 1987 criteria and 826 patients fulfilling the 2010 criteria, included in the Leiden Early Arthritis Clinic (EAC) between 1993-2008 to ascertain 10-years of follow-up. Mortality data were obtained from the civic registries (June 2018). Standardized-mortality-ratios (SMRs) were adjusted for age, gender and calendar-year, and additionally stratified for ACPA-positivity (anti-CCP2, cut-off&gt;10 mg/L) and DMARD-treatment. Results The contemporary UA-population was for 93% ACPA-negative and the SJC was 1 (median) and TJC 2. This presentation was milder than that of patients with conventional UA. In RA (both 1987-RA and 2010-RA) we observed excess mortality compared to the general population (Figure 1). In conventional UA, a trend towards excess mortality was observed: SMR 1.11 (95%CI:0.96-1.27). However, part of this UA population is currently classified as 2010-RA. Subsequently, in contemporary UA, which does not include these 2010 RA-patients, no excess mortality was observed: SMR 1.05 (95%CI:0.87-1.26). ACPA-stratification suggested excess mortality in ACPA-positive contemporary UA, but not in ACPA-negative contemporary UA (Figure 1). Mortality rates in contemporary UA-patients who did and did not receive DMARD-treatment were comparable (SMR 0.93 (95%CI:0.66-1.24) and SMR 1.08 (95%CI:0.82-1.36)). Figure 1. SMRs in UA and RA-patients with minimally 10-years of follow-up. Additionally, mortality was stratified for ACPA-status. In RA, SMRs were also stratified for early treat-to-target DMARD-therapy, which has been shown relevant for mortality analysis in RA. 3 ACPA: anticitrullinated autoantibody protein, UA: undifferentiated arthritis, RA: rheumatoid arthritis, SMR: Standardized mortality rate, IT: intensive treatment. Conclusion Contemporary UA has no excess mortality, in contrast to RA. So, besides milder disease at presentation within contemporary UA, also the long-term outcome mortality is more favorable and comparable to the general population. This supports the notion that contemporary UA-patients have intrinsically different characteristics than RA-patients, rather than representing an early stage of RA. Future studies are warranted to determine whether contemporary UA should be treated as RA; our results suggest that this population may deserve separate guidelines. References [1]T.W.J. Huizinga et al. Criteria for early rheumatoid arthritis: From Bayes’ law revisited to new thoughts on pathogenesis. Arthritis &amp; Rheumatism 2002. [2]Verstappen et al. Undifferentiated arthritis: a changing population who did not benefit from enhanced DMARD-strategies – results from a 25-years longitudinal inception cohort. Oxford rheumatology 2021. [3]Matthijssen et al. Early intensive treatment normalizes excess mortality in ACPA-negative RA, but not in ACPA-positive RA. Ann Rheum Dis 2020: Disclosure of Interests None declared.